Brain Communications, 2021
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Abstract White matter microstructure undergoes progressive changes during the lifespan, but the neurobiological underpinnings related to aging and disease remains unclear. We used an advanced diffusion MRI, Neurite Orientation Dispersion and Density Imaging (NODDI), to investigate the microstructural alterations due to demographics, common age-related pathological processes (amyloid, tau, and white matter hyperintensities), and cognition. We also compared NODDI findings to the older Diffusion Tensor Imaging model-based findings. 328 participants (264 cognitively unimpaired, 57 mild cognitive impairment, and 7 dementia with a mean age of 68.3 ±13.1 years) from the Mayo Clinic Study of Aging with multi-shell diffusion imaging, fluid attenuated inversion recovery MRI as well as amyloid and tau PET scans were included in this study. White matter tract level diffusion measures were calculated from Diffusion Tensor Imaging and NODDI. Pearson correlation and multiple linear regression analyses were performed with diffusion measures as the outcome and age, sex, education/occupation, white matter hyperintensities, amyloid, and tau as predictors. Analyses were also performed with each diffusion MRI measure as a predictor of cognitive outcomes. Age and white matter hyperintensities were the strongest predictors of all white matter diffusion measures with low associations with amyloid and tau. However, neurite density decrease from NODDI was observed with amyloidosis specifically in the temporal lobes. White matter integrity (mean diffusivity and free water) in the corpus callosum showed the greatest associations with cognitive measures. All diffusion measures provided information about white matter aging and white matter changes due to age-related pathological processes and were associated with cognition. NODDI and Diffusion Tensor Imaging are two different diffusion models that provide distinct information about variation in white matter microstructural integrity. NODDI provides additional information about synaptic density, organization, and free water content which may aid in providing mechanistic insights into disease progression.